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Enclosing a drug in a tiny liquid-filled microballoon, a process called microencapsulation has been shown to provide better drug delivery and new medical treatments for solid tumors and resistant infections. Multilayer microcapsules may hold the key to improving techniques of drug delivery during chemotherapy treatment. A new microencapsulation process and experiment apparatus was developed and flown on the STS-95 mission in 1998. During Expedition Five, investigators will repeat the STS-95 experiments to encapsulate two different complementary drugs in the same microcapsule. Additional experiments will include encapsulation of drugs and magnetic trigger particles that will enable physicians to break open the microcapsules with diagnostic levels of magnetic fields applied externally to deliver a burst of drug into whatever tissues the microcapsules are deposited in.

Researchers from the Center for Space Power at Texas A & M University and NASA Johnson Space Center in Houston, Texas will use the Microencapsulation Electrostatic Processing System (MEPS) to produce microcapsules for studies of optimum size distribution, drug loading, and effects of low-level fluid shear during the encapsulation process.

These unique capsules, which resemble miniature liquid-filled balloons the size of blood cells, are designed to deliver FDA-approved, anti-cancer drugs by injection into main arteries leading to tumors.

For many cancer patients, chemotherapy is one of the most feared parts of treatment because it can be so debilitating. With large, solid tumors, however, a special type of chemotherapy currently in use is called transcatheter chemoemobilization. In this process, approximately five percent of the "normal" dose is placed directly into the tumor through a catheter in one of the many blood vessels that serve the tumor followed by an injection of Gelfoam particles. These particles then swell to block the blood vessels in and around the tumor so that the treatment does not prematurely "wash out" too fast and the blood supply to the tumor is reduced, aiding the work of the chemotherapy.

Multilayer microcapsules may hold the key to improving this type of treatment. A multilayer capsule can hold both a dose of an FDA-approved anti-tumor drug and a radio-contrast medium. This will allow doctors to use C-T radiographic images of the microcapsules to monitor the accumulation and distribution of the capsules in the tumor to be sure that all regions of the tumor receive optimum treatment. The NASA-type microcapsules are made larger than white blood cells so they will block the tiny capillary arteries thereby blocking the blood vessels of the tumor -- reducing the blood supply to tumor cells — and providing sustained release of the anti-tumor drug inside the tumor itself.

The experiment is sponsored by NASA's Biological Systems Office at the Johnson Space Center and flown under the Space Product Development Office of the Microgravity Research Program at the Marshall Space Flight Center in Huntsville, Ala.

Experiment Summary

The Microencapsulation Electrostatic Processing System (MEPS) is an automated apparatus designed to form multi-layered, liquid-filled, microcapsules containing pharmaceuticals. The MEPS automated operations bring together two liquids — incapable of mixing — in such a way that it spontaneously causes the liquid-filled microcapsules to form as tiny liquid-filled bubbles that are surrounded by a thin, semi- permeable outer membrane.

After the microcapsules are formed and cured, the MEPS process filters out the microcapsules, washes them, and harvests them by pumping them into a reservoir. In some experiments, after rinsing, the MEPS process re-suspends the microcapsules in a special coating solution, then a high voltage electrostatic field is applied to the suspension; causing the coating material to rapidly deposit on the outer surface. The coatings of microcapsules are designed to give the microcapsules a specific surface charge that makes them less recognizable by immune cells in the blood stream. After coating they are harvested by pumping them into a separate storage reservoir until return to Earth. An average MEPS experiment takes about two hours.

Hardware/Operations

Hardware for the MEPS experiment consists of a chamber housing that holds self-contained process chamber modules, a video monitor/ recorder, an internal process control computer which controls the opening and closing of valves, fluid pumping, and a front control panel. Up to 10 experiments — each in a separate Process Chamber Module — will fly on each mission. The built-in video microscope monitors and records the critical stages of the process.

Background/Flight History

The first flight of the Microgravity Encapsulation Process System (MEPS) was on Space Shuttle mission STS-95 in the Spacehab. The experiments conducted on STS-95 included three specific manufacturing objectives:

Study the formation of microcapsules containing two kinds of anti-tumor drugs;

Micro-encapsulation of a photo-activated drug which, when exposed to infrared light will destroy surrounding tumors;

Study the process of applying electrostatic coatings to anti-tumor microcapsules to alter their surface charge enabling attachment of tumor targeting molecules on the outer surface of the microcapsules.

STS-95 verified the new microencapsulation processes, allowed larger quantities of microcapsules to be produced, and demonstrated how electrostatic coatings could be applied to the capsules.

The six flight experiments conducted on STS-95 included: 1) formation of anti-tumor microcapsules containing more than one drug for chemoembolization into the tumor, 2) formation of microcapsules containing a photo-activated drug which can be used for photo-dynamic therapy — activation with near-infrared light, and 3) electrostatic coating of anti-tumor microcapsules with a thin outer layer which can reduce the attack of immune cells and increase the chances of it reaching target tumors.

Benefits

Microgravity — the low gravity experienced in Earth-orbit — research has helped develop microcapsules that are significantly larger and carry more drug than those produced on Earth. Space experiments have led to improvements in drug formulations and to the development of commercial microcapsulation research. Experiments such as this could eventually lead to the development of anti-tumor drugs that allow the delivery of higher doses of chemotherapeutic drugs to specific treatment sites, reducing the unwanted side effects experienced by cancer patients.

Four U.S. Patents have been issued since 1998, based on the technology developed from the previous space experiments, and two more U.S. Patents have been approved for issue in 2002. NASA and Texas A & M University are seeking commercial partners to develop new applications for these unique microcapsules, new medical therapy approaches, and improvements in the microencapsulation process for larger scale-up production on Earth.

Additional Information/Photos

Additional information on Expedition Five and this experiment can be found at: